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Hospital Stay and Mortality Are Increased in Patients
Having a “Triple Low” of Low Blood Pressure, Low
Bispectral Index, and Low Minimum Alveolar
Concentration of Volatile Anesthesia
Daniel I. Sessler, M.D.,* Jeffrey C. Sigl, Ph.D.,† Scott D. Kelley, M.D.,‡ Nassib G. Chamoun, M.S.,§
Paul J. Manberg, Ph.D.,储 Leif Saager, M.D.,# Andrea Kurz, M.D.,** Scott Greenwald, Ph.D.††


What We Already Know about This Topic
• Anesthesiologists continue to refine factors associated with
morbidity and mortality after surgery.
• It is hoped identification of such factors will lead to treatments
that may greatly reduce adverse outcomes during the perioperative period.

Background: Low mean arterial pressure (MAP) and deep
hypnosis have been associated with complications and mortality. The normal response to high minimum alveolar concentration (MAC) fraction of anesthetics is hypotension and
low Bispectral Index (BIS) scores. Low MAP and/or BIS at
lower MAC fractions may represent anesthetic sensitivity.
The authors sought to characterize the effect of the triple low
state (low MAP and low BIS during a low MAC fraction) on
duration of hospitalization and 30-day all-cause mortality.
Methods: Mean intraoperative MAP, BIS, and MAC were
determined for 24,120 noncardiac surgery patients at the
Cleveland Clinic, Cleveland, Ohio. The hazard ratios associated with combinations of MAP, BIS, and MAC values

What This Article Tells Us That Is New
• In this retrospective review of a large database from a single
institution, the occurrence of low mean arterial pressure during
low minimum alveolar concentration fraction was a strong and
highly significant predictor for mortality, and when combined
with low bispectral index, the mortality risk was even greater.
Additional studies are needed to validate the triple low as an
indicator of perioperative mortality.

* Michael Cudahy Professor and Chair, # Assistant Professor,
** Professor and Vice-chair, Department of OUTCOMES RESEARCH,
Cleveland Clinic, Cleveland, Ohio. † Director, Analytical Research,
‡ Chief Medical Officer, Respiratory and Monitoring Solutions,
†† Senior Director, Advanced Research, Covidien, Inc., Dublin,
Ireland. § Chair, Lown Cardiovascular Research Foundation, Boston, Massachusetts; Adjunct Staff, Department of OUTCOMES RESEARCH, Cleveland Clinic. 储 Vice President, Clinical Research and
Regulatory Strategy, Covidien. Currently: Corolla Clin-Reg Consulting, Corolla, North Carolina.
Received from the Department of OUTCOMES RESEARCH, Cleveland
Clinic, Cleveland, Ohio; Covidien, Inc., Dublin, Ireland; Lown Cardiovascular Research Foundation, Boston, Massachusetts. Submitted for publication June 1, 2011. Accepted for publication March 6,
2012. Supported by Aspect Medical Systems, Norwood, Massachusetts. Aspect was recently acquired by Covidien, Dublin, Ireland.
The study was designed and conducted collaboratively by investigators from both organizations. Covidien employees have a financial interest in their company, but none of the Cleveland Clinic
authors has a personal financial interest in this research. Covidien
loaned some bispectral index monitors to the Cleveland Clinic.
Address correspondence to Dr. Sessler: Department of OUTCOMES
RESEARCH, Anesthesiology Institute, The Cleveland Clinic—P77,
Cleveland, Ohio 44195. This article may be accessed
for personal use at no charge through the Journal Web site,

greater or less than a reference value were determined. The
authors also evaluated the association between cumulative
triple low minutes, and excess length-of-stay and 30-day
Results: Means (⫾SD) defining the reference, low, and high
states were 87 ⫾ 5 mmHg (MAP), 46 ⫾ 4 (BIS), and 0.56 ⫾
0.11 (MAC). Triple lows were associated with prolonged
length of stay (hazard ratio 1.5, 95% CI 1.3–1.7). Thirty-day
mortality was doubled in double low combinations and quadrupled in the triple low group. Triple low duration ⱖ60
min quadrupled 30-day mortality compared with ⱕ15 min.
Excess length of stay increased progressively from ⱕ15 min
to ⱖ60 min of triple low.
Conclusions: The occurrence of low MAP during low
MAC fraction was a strong and highly significant predictor
䉫 This article is featured in “This Month in Anesthesiology.”
Please see this issue of ANESTHESIOLOGY, page 9A.
䉬 This article is accompanied by an Editorial View. Please see:
Kheterpal S, Avidan MS: “Triple low”: Murderer, mediator, or
mirror. ANESTHESIOLOGY 2012; 116:1176 – 8.

Copyright © 2012, the American Society of Anesthesiologists, Inc. Lippincott
Williams & Wilkins. Anesthesiology 2012; 116:1195–203

Anesthesiology, V 116 • No 6


June 2012